BACKGROUND & AIMS: INTRODUCTION:To obtain strict glucose regulation, an accurate and feasible bedside glucometry method is essential. We evaluated three different types of point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The study was performed as a single-centre, prospective, observational study in a 12-bed medical ICU of a university hospital. METHODS:Patients with an expected ICU stay of more than 48 hours were included. Because the reference laboratory delivers glucose values after approximately 30 to 60 minutes, which is too slow to use in a glucose regulation protocol and for calibration of the subcutaneous continuous glucose monitoring system (CGMS) (CGMS System Gold), we first validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study). Subsequently, part 2 was performed: after inserting (and calibrating) the subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial line every 6 hours and analysed on both the Precision PCx point-of-care meter using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data were downloaded after 24 to 72 hours. The results of the paired measurements were analysed as a scatter plot by the method of Bland and Altman and were expressed as a correlation coefficient. RESULTS:Part 1: Four hundred and twenty-four blood samples were drawn from 45 critically ill ICU patients. The ICU-based blood gas/glucose analyser ABL715 provided a good estimate of conventional laboratory glucose assessment: the correlation coefficient was 0.95. In the Clarke error grid, 96.8% of the paired measurements were in the clinically acceptable zones A and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU patients. The Precision PCx point-of-care meter showed a correlation coefficient of 0.89. Ninety-eight point seven percent of measurements were within zones A and B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89. One hundred percent of measurements were within zones A and B. CONCLUSION:The ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for laboratory glucose determination and can serve as a standard for ICU blood glucose measurements. The Precision PCx is a good alternative, but feasibility may be limited because of the blood sample handling. The subcutaneous CGMS System Gold is promising, but real-time glucose level reporting is necessary before it can be of clinical use in the ICU. When implementing a glucose-insulin algorithm in patient care or research, one should realise that the absolute glucose level may differ systematically among various measuring methods, influencing targeted glucose levels.

背景与目标： 简介：要获得严格的葡萄糖调节，准确，可行的床旁血糖测定方法必不可少。我们评估了重症重症监护病房（ICU）患者的三种不同的即时护理血糖仪。该研究是在大学医院的12张病床的ICU中进行的单中心，前瞻性，观察性研究。
方法：包括预期ICU超过48小时的患者。由于参考实验室在大约30至60分钟后会提供葡萄糖值，这太慢了，无法用于葡萄糖调节方案以及皮下连续葡萄糖监测系统（CGMS）（CGMS System Gold）的校准，因此我们首先验证了ICU-血气/葡萄糖分析仪ABL715（研究的第1部分）。随后，执行第2部分：插入（并校准）皮下CGMS后，每6小时从一条动脉管线中抽取肝素化的动脉血样本，并在Precision PCx即时检测仪上使用试纸条和血液进行分析气体/葡萄糖分析仪ABL715。 CGMS葡萄糖数据在24到72小时后下载。配对测量的结果通过Bland和Altman方法作为散点图进行分析，并表示为相关系数。
结果：第1部分：从45名重症ICU患者中抽取了242份血液样本。基于ICU的血气/葡萄糖分析仪ABL715提供了常规实验室葡萄糖评估的良好估计：相关系数为0.95。在Clarke误差网格中，96.8％的配对测量值在临床上可接受的区域A和B中。第2部分：从19位ICU患者中抽取了165个配对样品。 Precision PCx即时护理仪的相关系数为0.89。百分之九十八的测量值在区域A和B内。皮下CGMS系统Gold的相关系数为0.89。百分之一百的测量值在区域A和B内。
结论：基于ICU的血糖分析仪ABL715是一种快速准确的实验室葡萄糖测定方法，可作为ICU血糖测量的标准。 Precision PCx是一个很好的选择，但由于血液样本的处理，可行性可能受到限制。皮下CGMS System Gold前景看好，但在ICU中临床应用之前，必须实时报告葡萄糖水平。在患者护理或研究中实施葡萄糖-胰岛素算法时，应认识到，各种测量方法之间的绝对葡萄糖水平可能会系统地不同，从而影响目标血糖水平。

BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

背景与目标： 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖，但需要（i）通过位于外围的组成型葡萄糖脱氢酶（对渗透压休克不敏感）将其氧化为D-葡萄糖酸，（ii）D-葡萄糖酸在D.葡萄糖中的积累（iii）诱导负责摄取D-葡萄糖酸的特定能量依赖性转运系统。该摄取系统显示了在30 mC，pH 7.0的50 mM磷酸钾缓冲液中的最大运输速率。在这些条件下，D-葡萄糖酸的K（m）计算值为6.7 microM。此外，还发现了一个专门针对葡萄糖吸收的不同转运系统。它是有活性的，在35 m的50 mM磷酸钾缓冲液（pH 6.0）中显示最大吸收速率，K（m）值为8.3 microM。

BACKGROUND & AIMS: OBJECTIVES:There are no direct comparisons of blood glucose values in samples collected with barrier serum tubes (SST) and NaF/potassium oxalate (NaF/KOx) plasma tubes. Collection of samples in SST tubes can offer considerable savings and specimen processing advantages for national level surveys. DESIGN AND METHODS:Serum and plasma samples were collected under 'field conditions' from a single draw of 3692 individuals participating in the Canadian Health Measures Survey. The samples were analyzed retrospectively using the VITROS GLU Slide method (glucose oxidase-based). RESULTS:There was a high rate of hemolysis in the NaF/KOx tubes (86.2%) while hemolysis was infrequently observed with the SST tubes (2%). Comparing only blood draws where no hemolysis was observed in both tubes (n=495; paired t-test) showed no effect of tube type on serum/plasma glucose concentrations. This was also observed when data was restricted to cases when only SST samples were not hemolyzed (n=3546; paired t-test). CONCLUSIONS:These data show that both collection tubes can be used under survey collection and processing conditions to measure glucose with our assay system with no difference in reported results.

背景与目标： 目的：尚无直接比较采用屏障血清试管（SST）和NaF /草酸钾（NaF / KOx）血浆试管收集的样本中血糖值的方法。在SST管中收集样品可以为国家级调查提供大量的节省和样品处理的优势。
设计与方法：在“现场条件”下从参加加拿大卫生措施调查的3692个人中抽取了血清和血浆样品。使用VITROS GLU Slide方法（基于葡萄糖氧化酶）对样品进行回顾性分析。
结果：NaF / KOx管的溶血率很高（86.2％），而SST管的溶血率很少（2％）。仅比较在两个试管中均未观察到溶血的抽血情况（n = 495；配对t检验）显示试管类型对血清/血浆葡萄糖浓度无影响。当数据仅限于仅不对SST样品进行溶血的情况时（n = 3546；配对t检验），也可以观察到这一点。
结论：这些数据表明，在我们的测定系统中，两个收集管均可在调查收集和处理条件下用于测量葡萄糖，报道的结果没有差异。

BACKGROUND & AIMS: :The objective of this study was to evaluate the effects of ultrasound-mediated analyte diffusion on permeability of normal, benign, and cancerous human lung tissue in vitro and to find more effective sonophoretic (SP) delivery in combination with the optical clearing agents (OCAs) method to distinguish normal and diseased lung tissues. The permeability coefficients of SP in combination with OCAs diffusion in lung tissue were measured with Fourier-domain optical coherence tomography (FD-OCT). 30% glucose and SP with a frequency of 1 MHz and an intensity of 0.80  W/cm2 over a 3 cm probe was simultaneously applied for 15 min. Experimental results show that the mean permeability coefficients of 30% glucose/SP were found to be (2.01±0.21)×10(-5)  cm/s from normal lung (NL) tissue, (2.75±0.28)×10(-5)  cm/s from lung benign granulomatosis (LBG) tissue, (4.53±0.49)×10(-5)  cm/s from lung adenocarcinoma tumor (LAT) tissue, and (5.81±0.62)×10(-5)  cm/s from lung squamous cell carcinoma (LSCC) tissue, respectively. The permeability coefficients of 30% glucose/SP increase approximately 36.8%, 125.4%, and 189.1% for the LBG, LAT, and LSCC tissue compared with that for the NL tissue, respectively. There were statistically significant differences in permeability coefficients of 30% glucose/SP between LBG and NL tissue (p<0.05), between LAT and NL tissue (p<0.05), and between LSCC and NL tissue (p<0.05). The results suggest that the OCT functional imaging technique to combine an ultrasound-OCAs combination method could become a powerful tool in early diagnosis and monitoring of changed microstructure of pathologic human lung tissue.

背景与目标： ：这项研究的目的是评估超声介导的分析物扩散对正常，良性和癌性人肺组织的体外渗透性的影响，并与光学清除剂（OCA）结合发现更有效的超声导入（SP）方式）区分正常和患病肺组织的方法。用傅里叶域光学相干断层扫描（FD-OCT）测量SP的渗透系数以及OCA在肺组织中的扩散。同时在3 cm探针上施加30％的葡萄糖和SP，频率为1 MHz，强度为0.80 W / cm2，持续15分钟。实验结果表明，与正常肺组织相比，30％葡萄糖/ SP的平均渗透系数为（2.01±0.21）×10（-5）cm / s，（2.75±0.28）×10（-5）肺良性肉芽肿病（LBG）组织的cm / s，肺腺癌肿瘤（LAT）组织的（4.53±0.49）×10（-5）cm / s和（5.81±0.62）×10（-5）cm /分别来自肺鳞状细胞癌（LSCC）组织。与NL组织相比，LBG，LAT和LSCC组织的30％葡萄糖/ SP的渗透系数分别增加了约36.8％，125.4％和189.1％。 LBG和NL组织之间（p <0.05），LAT和NL组织之间（p <0.05）以及LSCC和NL组织之间（p <0.05）的30％葡萄糖/ SP的通透性系数在统计学上有显着差异。结果表明，OCT功能成像技术结合超声-OCAs组合方法可能成为早期诊断和监测病理性人肺组织微观结构变化的有力工具。

BACKGROUND & AIMS: :Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.

背景与目标： 饮食和情感障碍之间的关系仍然复杂且不清楚。厌食症患者的脑葡萄糖代谢已被证实在全球和区域均降低，顶叶皮层中存在特定的相对低代谢。为了探索减肥或抑郁症状对脑代谢的可能影响，我们研究了年龄和性别相匹配的低体重厌食症和抑郁症患者，正常体重的抑郁症患者以及健康志愿者。低体重患者的全球和区域绝对葡萄糖活性水平降低，而厌食患者的葡萄糖水平最低。在相对价值方面，与对照组相比，厌食患者的顶叶代谢明显降低，而尾核中的新陈代谢较其他组更高。葡萄糖的绝对低代谢似乎是低体重的结果，因为它在低体重厌食症患者和低体重抑郁症患者中均被发现。另外，在所有受试者中，绝对葡萄糖值与体重指数显着相关。未来精神病患者的正电子发射断层扫描研究应控制饮食参数。

BACKGROUND & AIMS: BACKGROUND:Control of hyperglycemia in adult medical and surgical intensive care units (ICUs) has been shown to dramatically decrease morbidity and mortality. Algorithms to achieve glycemic control in the ICU setting are evolving. We have evaluated the use of a discrete proportional-integral-derivative (PID) algorithm to control hyperglycemia in pediatric ICU (PICU) patients both with and without diabetes. METHODS:Six PICU patients [four with diabetic ketoacidosis (DKA) and two with glucocorticoid-induced hyperglycemia] with glucose values >150 mg/dL were enrolled. Their hyperglycemia was managed with a PID algorithm that provided recommendations for both changes in the intravenous insulin infusion rate and the time to obtain the next discrete glucose value. Glucose targets were adjusted based on clinical circumstances. RESULTS:Patients (mean age 9.2 years; range 1.8-14 years) utilized the algorithm for a total of 454.4 h. Mean time to the initial glucose target was 8.7 h (range 1.3-15.1 h) in five patients. One subject with hyperosmolar DKA did not achieve target before discharge from the PICU, and another was at target when the algorithm was initiated. After the glucose target was achieved, the mean SD was 23.5 mg/dL, and glucose values were >40 mg/dL above target 13% of the time and <40 mg/dL below target 1% of the time. There were no glucose values <55 mg/dL. CONCLUSION:The PID algorithm safely and effectively controlled hyperglycemia in a PICU, despite multiple changes in intravenous fluids, steroid doses (including high-dose pulses), and hemodialysis.

背景与目标： 摘要背景：控制成人医学和外科重症监护病房（ICU）的高血糖症已显着降低发病率和死亡率。在ICU设置中实现血糖控制的算法正在不断发展。我们评估了使用离散比例积分微分（PID）算法来控制有或没有糖尿病的小儿ICU（PICU）患者的高血糖。
方法：招募了6例PICU患者[其中4例患有糖尿病酮症酸中毒（DKA），2例患有糖皮质激素引起的高血糖症]，其血糖值> 150 mg / dL。他们的高血糖症通过PID算法进行管理，该算法为静脉内胰岛素输注速率的变化以及获得下一个离散葡萄糖值的时间提供了建议。根据临床情况调整葡萄糖靶标。
结果：患者（平均年龄9.2岁；范围1.8-14岁）使用该算法的时间总计为454.4小时。五名患者达到初始血糖目标的平均时间为8.7小时（范围1.3-15.1小时）。高渗性DKA的一名受试者在未从PICU出院前未达到目标，另一名受试者在算法启动时就达到了目标。达到葡萄糖目标后，平均SD为23.5 mg / dL，并且葡萄糖值在目标时间的13％之上大于40 mg / dL，在目标时间的1％以下小于40 mg / dL。没有葡萄糖值＜55mg / dL。
结论：尽管静脉输液，类固醇剂量（包括大剂量脉搏）和血液透析发生了多种变化，PID算法仍可安全有效地控制PICU中的高血糖。

BACKGROUND & AIMS: AIM:This study assessed whether the poor correlation between HbA1c and oral glucose tolerance test (OGTT) for dysglycaemia diagnosis may be explained by haemoglobin glycation (HbG). METHODS:A total of 1033 consecutive overweight or obese patients with no known diabetes underwent OGTT and measurement of HbA1c to diagnose diabetes and dysglycaemia (American Diabetes Association criteria). For each OGTT result category, low, medium and high HbG was defined according to the mean HbA1c/fructosamine ratio and mean fructosamine. High HbG was defined as values greater than mean values in each OGTT category for both HbA1c/fructosamine ratio and fructosamine levels, and low HbG was defined as lower values of both. The remaining patients were considered medium HbG. RESULTS:Based on OGTT and HbA1c values, 267 (25.8%) and 443 (42.8%) patients had intermediate hyperglycaemia, and 66 (6.4%) and 95 (9.2%) patients had diabetes, respectively. The results were discordant for intermediate hyperglycaemia or diabetes diagnosis in 41.7% and for diabetes diagnosis in 10.0% of the patients. The proportion of patients with HbA1c≥6.5%, but without OGTT-diagnosed diabetes, was 0%, 3.8% and 32.8% in the low-HbG, medium-HbG and high-HbG groups, respectively. In contrast, the proportion of patients with HbA1c<5.7%, but with an abnormal OGTT, was 30.4%, 11.1% and 0%, respectively. The AUROC of HbA1c to detect OGTT-diagnosed diabetes was better in the medium-HbG group [0.874 (0.816-0.931)] than in those with low or high HbG [0.628 (0.489-0.768); P<0.01]. Only age was independently associated with high-HbG status [10-year OR: 1.3 (1.1-1.5); P<0.0001]. CONCLUSION:Haemoglobin glycation may explain many of the discordant results between HbA1c and OGTT when used for dysglycaemia diagnosis.

背景与目标： 目的：该研究评估了HbA1c与口服葡萄糖耐量试验（OGTT）诊断血糖异常之间的不良关联是否可以通过血红蛋白糖化（HbG）来解释。
方法：总共1033例不明糖尿病的连续超重或肥胖患者接受OGTT并测量HbA1c以诊断糖尿病和血糖异常（美国糖尿病协会标准）。对于每个OGTT结果类别，根据平均HbA1c /果糖胺比率和平均果糖胺定义低，中和高HbG。高HbG定义为HbA1c /果糖胺比率和果糖胺水平在每个OGTT类别中均大于平均值，而低HbG定义为两者均较低。其余患者被认为是中等HbG。
结果：基于OGTT和HbA1c值，分别有267例（25.8％）和443例（42.8％）的患者出现中度高血糖，分别为66例（6.4％）和95例（9.2％）的糖尿病。结果与41.7％的中度高血糖或糖尿病诊断和10.0％的患者的糖尿病诊断不一致。低HbG，中HbG和高HbG组中HbA1c≥6.5％但无OGTT诊断的糖尿病的患者比例分别为0％，3.8％和32.8％。相反，HbA1c <5.7％但OGTT异常的患者比例分别为30.4％，11.1％和0％。在中等HbG组[0.874（0.816-0.931）]中，HbA1c的AUROC检测OGTT诊断的糖尿病要好于HbG较低或较高[0.628（0.489-0.768）]。 P ＜0.01]。只有年龄与高HbG状况独立相关[10年OR：1.3（1.1-1.5）； P <0.0001]。
结论：血红蛋白糖基化可解释HbA1c和OGTT在诊断血糖异常中的许多不一致结果。

BACKGROUND & AIMS: :Chronic exposure to high glucose leads to diabetic nephropathy characterized by increased mesangial matrix protein (e.g., collagen) accumulation. Altered cell signaling and gene expression accompanied by oxidative stress have been documented. The contribution of the tyrosine kinase, c-Src (Src), which is sensitive to oxidative stress, was examined. Cultured rat mesangial cells were exposed to high glucose (25 mmol/L) in the presence and absence of Src inhibitors (PP2, SU6656), Src small interfering RNA (siRNA), and the tumor necrosis factor-α-converting enzyme (TACE) inhibitor, TAPI-2. Src was investigated in vivo by administration of PP2 to streptozotocin (STZ)-induced diabetic DBA2/J mice. High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. Thus, Src may provide a novel therapeutic target for diabetic nephropathy.

背景与目标： ：长期暴露于高葡萄糖会导致糖尿病肾病，其特征是肾小球系膜基质蛋白（例如胶原蛋白）蓄积增加。已经记录了改变的细胞信号传导和基因表达并伴有氧化应激。检查了对氧化应激敏感的酪氨酸激酶c-Src（Src）的贡献。在存在和不存在Src抑制剂（PP2，SU6656），Src小干扰RNA（siRNA）和肿瘤坏死因子-α转化酶（TACE）的情况下，将培养的大鼠肾小球系膜细胞暴露于高葡萄糖（25 mmol / L）抑制剂，TAPI-2。通过对链脲佐菌素（STZ）诱导的糖尿病DBA2 / J小鼠施用PP2在体内研究了Src。高葡萄糖刺激的Src，TACE，表皮生长因子受体（EGFR），有丝分裂原激活的蛋白激酶（MAPK），细胞外信号调节激酶（ERK1 / 2，p38）和胶原IV在肾小球膜细胞中的蓄积。 PP2和SU6656阻止了Src Tyr-416，EGFR和MAPK的高葡萄糖刺激磷酸化。这些抑制剂和siRNA以及SAPI敲除的Src敲除也废除了高葡萄糖诱导的这些靶标的磷酸化和胶原IV的积累。在STZ糖尿病小鼠中，白蛋白尿，Src pTyr-416升高，TACE活化，ERK和EGFR磷酸化，肾小球胶原蛋白积聚和足细胞丢失均被PP2抑制。这些数据表明Src在高葡萄糖-Src-TACE-肝素结合表皮生长因子-EGFR-MAPK信号通路中积累胶原蛋白的作用。因此，Src可以为糖尿病性肾病提供新的治疗靶标。

BACKGROUND & AIMS: :Abstract Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate.

背景与目标： 摘要：已发现葡萄糖会削弱阿司匹林对血小板的抑制作用，并改变血小板中一氧化氮合酶（NOS）的基础活性。这项工作的目的是研究葡萄糖对活化血小板抑制途径的影响。葡萄糖的短期温育削弱了由激活NOS依赖性途径的药物（如L-精氨酸，腺苷和α-生育酚）诱导的血小板凝集抑制作用。但是，葡萄糖对伊洛前列素和BW245C所诱导的抑制作用没有影响，伊洛前列素和BW245C可以激活环磷酸腺苷（cAMP）信号通路。乳酸钾减弱了与葡萄糖相同的抑制剂的作用。葡萄糖转运的抑制剂阻止了葡萄糖的作用。众所周知，二氯乙酸盐可防止丙酮酸转化为乳酸盐并减少血小板中的乳酸盐，从而大大减弱了葡萄糖在血小板中的作用。数据支持这样的建议，即葡萄糖对乳酸的影响是通过激活NOS依赖性途径的药物对血小板的抑制作用。

BACKGROUND & AIMS: AIMS/HYPOTHESIS:Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. METHODS:Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. RESULTS:Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p < 0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups. CONCLUSIONS/INTERPRETATION:Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT01680133.

背景与目标： 目的/假设：脂解作用的调节受损和脂质中间体的积累可能会导致肥胖相关的胰岛素抵抗和2型糖尿病。我们调查了胰岛素抵抗正常的肥胖男性和2型糖尿病男性肥胖者的腹部皮下脂肪组织（AT）和骨骼肌（SM）的胰岛素介导的脂解抑制作用。
方法：11名NGT男性和9名经长期诊断的2型糖尿病男性（7±1岁），年龄相匹配（58±2 vs 62±2岁），BMI（31.4±0.6 vs 30.5±0.6 kg / m（2） ）和[公式：参见文字]（28.9±1.5 vs 29.5±2.4 ml kg（-1）min（-1））参与了这项研究。在1 h的基础期和6 h的逐步高胰岛素血症-正常血糖钳制（8、20和40 mU m（-2）min（-1））中使用微透析法评估AT和SM中的间质甘油浓度。收集AT和SM活组织检查以研究潜在的机制。
结果：与NGT男性（-21±7％，-38±8）相比，高胰岛素血症抑制的2型糖尿病男性的间质SM甘油浓度更低（-7±6％，-13±9％和-27±9％） ％和-53±8％）（p = 0.014）。这伴随着循环脂肪酸和甘油浓度的增加，葡萄糖输注速率的降低（21.8±3.1 vs 30.5±2.0μmolkg体重（-1）min（-1）; p <0.05），激素敏感性脂肪酶更高（ HSL）丝氨酸660磷酸化，2型糖尿病男性患者与NGT男性相比，肌肉膜中饱和二酰基甘油（DAG）脂质种类增加，蛋白激酶C（PKC）活化增加。两组之间在胰岛素介导的AT间质甘油减少方面没有观察到显着差异。
结论/解释：我们的结果表明，胰岛素介导的SM脂解抑制作用减弱可能会促进膜饱和DAG的积累，加重胰岛素抵抗，至少部分是由PKC介导的。这可能代表了胰岛素抵抗向2型糖尿病发展的重要机制。
试用注册：ClinicalTrials.gov NCT01680133。

BACKGROUND & AIMS: :Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

背景与目标： ：蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素信号通路负调节的关键因素，可能在糖尿病和肥胖症中起重要作用。通过筛选用于糖尿病门诊的传统中草药提取物库，我们确定了熊果酸（一种普遍存在于传统中草药中的天然五环三萜类化合物）作为PTP1B抑制剂。通过修饰熊果酸，我们设计并合成了K（i）为283 nM的衍生物。作为PTP1B的竞争性抑制剂，熊果酸及其衍生物还抑制T细胞蛋白酪氨酸磷酸酶和src同源性磷酸酶2，但不抑制白细胞抗原相关的磷酸酶或蛋白酪氨酸磷酸酶α和epsilon，这些都可能与胰岛素途径有关。熊果酸衍生物增强CHO / hIR细胞中胰岛素受体的磷酸化，并刺激L6肌管中的葡萄糖摄取。

BACKGROUND & AIMS: INTRODUCTION:Basal leptin level has been demonstrated to correlate positively with many indices of obesity, as well as insulin resistance. However, to date, little is known about regulation of leptin in obese children with incipient glucose metabolic disorders. OBJECTIVE:The aim of this study was to define the precise influence of the glucose tolerance status on plasma leptin in obese boys and girls separately. MATERIAL AND METHODS:70 obese children with impaired glucose tolerance (IGT) and well-matched 70 normal glucose-tolerant (NGT) subjects were examined. Fasting and 2-h post glucose load plasma glucose and insulin levels as well as fasting leptin levels were determined, apart from anthropometric measurements. RESULTS:Leptin levels were significantly lower in girls with IGT compared to NGT girl (17.7+/-6.5 microg/L vs. 23.1+/-7.7 microg/L; p<.001). No such difference was observed in boys. In a multiple regression analysis adjusting for age and adiposity, in the female group plasma glucose and insulin levels 2-h after glucose load were the best predictors of fasting plasma leptin (r=-0.49, p<.005 and r=0.34, p<.05; respectively). In boys, plasma insulin level 2-h after glucose load was the independent determinant of leptin (r=0.36, p<.05). CONCLUSION:The differences between regulation of leptin synthesis in girls and boys with simple obesity were found. The stimulatory effect of insulin on leptin synthesis was greater in girls with normoglycemia than in girls with impaired glucose tolerance.

背景与目标： 简介：基础瘦素水平已被证明与许多肥胖指数以及胰岛素抵抗呈正相关。然而，迄今为止，关于肥胖儿童早期糖代谢紊乱中瘦素的调控知之甚少。
目的：本研究的目的是明确定义葡萄糖耐量状态对肥胖男孩和女孩血浆瘦素的精确影响。
材料与方法：检查了70名糖耐量受损（IGT）肥胖儿童和70名正常糖耐量（NGT）受试者的匹配性。除了人体测量之外，还测定了空腹和葡萄糖负荷后2小时的血浆葡萄糖，胰岛素水平以及空腹瘦素水平。
结果：IGT女孩的瘦素水平明显低于NGT女孩（17.7 /-6.5 microg / L vs. 23.1 /-7.7 microg / L； p <.001）。在男孩中没有观察到这种差异。在校正年龄和肥胖的多元回归分析中，在女性组中，葡萄糖负荷后2小时的血浆葡萄糖和胰岛素水平是空腹血浆瘦素的最佳预测指标（r = -0.49，p <.005，r = 0.34，p <.05;分别）。在男孩中，葡萄糖负荷后2小时的血浆胰岛素水平是瘦素的独立决定因素（r = 0.36，p <.05）。
结论：发现单纯性肥胖的男孩和女孩的瘦素合成调控存在差异。血糖正常的女孩胰岛素对瘦素合成的刺激作用大于葡萄糖耐量受损的女孩。

BACKGROUND & AIMS: OBJECTIVE:We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population. RESEARCH DESIGN AND METHODS:The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged > or =25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999-2000 and 5 years later in 2004-2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system. RESULTS:The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline. CONCLUSIONS:The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.

背景与目标： 目的：我们确定了澳大利亚人群样本中葡萄糖代谢与视网膜病变的纵向相关性。
研究设计与方法：澳大利亚糖尿病肥胖与生活方式研究（AusDiab）是一项全国纵向研究，研究对象是来自澳大利亚42个随机选择地区的25岁或以上的成年人。在1999-2000年和5年后的2004-2005年的基线时，对被鉴定为患有糖尿病（根据自我报告和口服葡萄糖耐量试验）和葡萄糖代谢受损的参与者以及随机抽取的葡萄糖耐量正常的参与者进行了视网膜病变评估。完整的视网膜数据可供1,192名参与者使用。根据简化版的威斯康星州评分系统，在两个时间点对照片进行了评分。
结果：在基线时已知和新诊断的糖尿病患者中，视网膜病变的5年发生率分别为13.9％和3.0％。在随访中发展为新诊断为糖尿病的人中，基线时有11.9％的视网膜病变，而未进展为新诊断为糖尿病的人为5.6％（P = 0.037）。在对确定为糖尿病危险因素的因素进行校正后，基线时视网膜病变征象的个体发生新近诊断出的糖尿病的可能性是基线时没有视网膜病变征象的个体的两倍。
结论：已知糖尿病患者的5年视网膜病变发生率为13.9％。基线时具有视网膜病变征象的非糖尿病患者在5年后患新诊断出的糖尿病的风险要高两倍。该结果提供了进一步的证据，表明轻度的视网膜病变征象可能是潜在的微血管疾病和未来糖尿病风险的临床前标志物。

BACKGROUND & AIMS: :Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones.

背景与目标： ：对12名因心脏骤停而导致的缺氧后综合征的患者进行了13次正电子发射断层扫描术，研究了脑葡萄糖利用情况。七名受试者处于持续的植物生长状态。其他5名受试者通常是有意识的，但有局灶性神经系统体征。当与正常值比较时，营养受试者的平均脑葡萄糖代谢急剧下降（+/- 50％），而意识清醒的患者的平均脑葡萄糖代谢降低程度较小（+/- 25％）。最一致的区域性改变是在顶枕皮层（9例），椎骨和颈动脉领土之间的边界，其次是额骨交界处（5例），纹状体（肌张力障碍3例），丘脑（2例）。 ）和视觉皮层（2例皮质失明）。这些数据表明，脑缺氧可导致整体脑代谢不足，这与警惕状态以及优先位于动脉边界区域的区域改变有关。

BACKGROUND & AIMS: :Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30-60 min and 60-120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats.

背景与目标： ：药用植物构成了糖尿病潜在治疗剂的重要来源。在本研究中，我们调查了辣木（MO）林，辣木对Wistar大鼠和Goto-Kakizaki（GK）大鼠（模型2型糖尿病）的葡萄糖耐量的影响。通过HPLC分析，MO粉末中的主要多酚是槲皮素葡糖苷，芦丁，山emp酚糖苷和绿原酸。作为葡萄糖耐量试验的结果，与给予葡萄糖后的两个对照组相比，MO显着降低了GK大鼠在20、30、45和60分钟时的血糖，而Wistar大鼠在10、30和45分钟时降低了血糖（p <0.05）。在30-60分钟和60-120分钟期间，GK对照组的血糖变化曲线下面积显着高于GK + MO组（p <0.05）。此外，MO显着降低了GK大鼠的胃排空（p <0.05）。结果表明，MO对葡萄糖不耐症具有改善作用，其作用可能是由槲皮素-3-葡萄糖苷和MO叶粉中的纤维含量介导的。 MO的作用在GK大鼠中比在Wistar大鼠中更大。